Persistent, use-dependent changes in synaptic efficacy, such as long-term potentiation (LTP), may play an essential role in the adaptive properties of the nervous system. We have recently discovered that LTP can be induced in the crayfish claw opener nerve-muscle system. The latter preparation is ideal for studying LTP because it is simple in structure, it offers numerous experimental advantages for both in vivo behavioral and in vitro biophysical studies, and it has many morphological and physiological features in common with synapses of the vertebrate central nervous system. The present proposal has three interrelatd objectives. The first goal is to demonstrate that the naturally occurring, endogenously-generated patterns of neuronal activity that occur in the excitator and inhibitor axons of unrestrained animals are sufficient to induce LTP. The second goal is to determine and quantify the conditions and laws governing the induction, persistence, and heterosynaptic modulation of LTP. The third goal is to provide evidence on the biophysical mechanism underlying LTP. Most of the experiments outlined in this proposal can be performed only on the opner nerve-muscle system and the results of this research should greatly enhance our knowledge of use-dependent, long-term synaptic plasticity.